The Relationship Between Immune Cells and Uterine Fibroids: A Bidirectional Mendelian Randomization Study

Xiaoxiao Deng; Shaoli Zhuang; Yanping Chen; Fangfang Chen; Zhang Zhang; Wu Chen

doi:10.2147/IJWH.S591986

The Relationship Between Immune Cells and Uterine Fibroids: A Bidirectional Mendelian Randomization Study

Int J Womens Health. 2026 Apr 18:18:591986. doi: 10.2147/IJWH.S591986. eCollection 2026.

Authors

Xiaoxiao Deng¹, Shaoli Zhuang¹, Yanping Chen¹, Fangfang Chen¹, Zhang Zhang¹, Wu Chen¹

Affiliation

¹ Department of Gynecology, The People's Hospital of Pingyang, Wenzhou, Zhejiang, 325400, People's Republic of China.

Abstract

Objective: This research applied a bidirectional Mendelian randomization (MR) framework to investigate potential two-way causal associations between immune cell phenotypes and uterine fibroids (UF).

Methods: This research drew upon publicly available data from large-scale genome-wide association studies (GWAS), encompassing 731 immune cell phenotypes from 3757 participants and UF data from 21,024 cases and 237,694 controls. Primary causal estimates were derived using the inverse-variance weighted (IVW) approach, with additional validation through MR-Egger, weighted median, and related methods. To ensure the reliability of the results, MR-PRESSO analysis, leave-one-out analysis, and false discovery rate (FDR) correction were also performed.

Results: Forward MR analyses initially identified 39 immune phenotypes significantly associated with UF (IVW P < 0.05), comprising 23 risk factors and 16 protective factors. Applying stringent selection criteria-IVW P < 0.001, consistent odds ratio (OR) directions across five analytical methods, and pleiotropy P > 0.05-three phenotypes demonstrated strong causal links with UF: CD39⁺ CD8⁺ T cells, CD25 expression on IgD^- CD27^- B cells, and HLA-DR expression on CD14⁺ CD16^- monocytes (all IVW P < 0.001). The reverse MR analysis indicated a negative causal effect of UF on the proportion of CD39⁺ CD8⁺ T cells (IVW OR = 0.895, P = 0.037). Sensitivity analyses ruled out interference from horizontal pleiotropy and heterogeneity, supporting the reliability of the study's conclusions. However, after FDR correction, none of the causal associations remained statistically significant.

Conclusion: Our research offers compelling genetic evidence supporting a forward causal link between CD39⁺ CD8⁺ T cells, CD25 on IgD^- CD27^- B cells, and HLA-DR on CD14⁺ CD16^- monocytes and UF, and a reverse causal link between CD39⁺ CD8⁺ T cells and UF, highlighting immune regulation as a potentially pivotal factor in UF pathogenesis.

Keywords: bidirectional mendelian randomization; causality; immune cells; inverse-variance weighted; uterine fibroids.